PB2496: CAR-T CELLS THERAPY COMBINED WITH POMALIDOMIDE AGAINST RELAPSE AND REFRACTORY MM OR ALL WITH EXTRAMEDULLARY INVOLVEMENT
Authors: Jie Zhao, Weiwei Tian
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: CAR-T cells targeting CD19 and BCMA are currently approved for the treatment of relapsed and refractory multiple myeloma (MM) and B-acute lymphoblastic leukaemia (B-ALL). However, CAR-T cells in patients with extramedullary involvement often relapse early and have a limited curative effect. In addition, CAR-T treatment followed by reinfusion of the same target CAR-T has a short duration in vivo. How to improve the efficacy and prolong the duration of CAR-T remains a pressing issue. Pomalidomide and radiotherapy can regulate the tumour microenvironment and may have a synergistic effect on the efficacy of CAR-T cells. This combined treatment strategy has not yet been reported Aims: Our study was designed to evaluate the efficacy and safety of CAR-T in combination with pomalidomide ± radiotherapy in relapsed and refractory MM/B-ALL with extramedullary infiltration. Methods: We reviewed the data of five patients who received CAR-T therapy for relapsed and refractory MM or B-ALL with extramedullary involvement and were admitted to Bethune Hospital in Shanxi, China from December 2020 to November 2022. All patients were treated with a combination of pomalidomide (2 patients received 2 mg on the first day after CAR-T transfusion, the rest received 1 mg when the CAR-T cell copy number decreased). 2 patients with heavily treated relapsed and refractory MM received additional local radiotherapy prior to CAR-T therapy. Results: We enrolled 5 patients with extramedullary infiltration, three of whom had relapsed and refractory MM, and the other two of whom had relapsed and refractory B-ALL. Three cases of relapsed and refractory MM: All patients received more than three lines of treatment, have been exposed to at least 2 proteasome inhibitors, 2 immunomodulators, CD38 monoclonal antibody, had previously been resistant to pomalidomide. All 3 patients had extramedullary soft tissue involvement, one of which was associated with central involvement. After treatment, One had a partial and 2 had a complete remission. One patient with central involvement achieved a complete remission with the addition of radiotherapy+BCMA+ pomalidomide, and one patient had an expansion peak with the addition of pomalidomide when the CAR-T copy number decreased. One patient had grade 1 CRS. Two cases of relapsed and refractory B-ALL: one patient with central infiltration and one with pericardial infiltration treated with CAR-T cells in the early stage. After extramedullary relapse, the same targeted CAR-T in combination with pomalidomide achieved complete remission. Both patients had grade 1 CRS. Summary/Conclusion We reported for the first time that CAR-T combined with pomalidomide±radiotherapy in relapsed and refractory MM/B-ALL with extramedullary involvement achieved good efficacy with tolerable side effects. CAR-T copy number amplification was observed after the combination. The current treatment combination provides a new strategy for relapse and refractory MM/B-ALL with extramedullary involvement. TABLE 1 Clinical information of the five patients with MM/B-ALL - Number Sex Age Diagnosis genetic alteration Invasion Number of prior therapies Dosage ofCAR-T cells Pomalidomide Efficacy evaluation CRS 1 Female 62 MM 1q21amp CNS 9 BCMA:3.25×106/ kg D1:2mg CR Level 1 2 Female 62 MM del 17p，1q21amp，t(4:14) Soft tissue 3 BCMA：5×106/ kg D37:1mg PR - 3 Female 65 MM 1q21amp Soft tissue 4 GPRC5D:1×106/ kg D12:1mg CR - 4 Female 26 Ph+B-ALL t(9;22) CNS 3 Sceond infusionCD19: 3.59×106/kgCD22: 4.13×106/kg D1:2mg CR Level 1 5 Female 16 B-ALL - pericardium 5 Sceond infusionCD19: 2×106/kgCD22: 2×106/kg D29:1mg CR Level 1 Keywords: CAR-T, Multiple myeloma, ALL